Arthritis remains the most prevalent cause of disability in the US. Rheumatoid arthritis is the most common autoimmune inflammatory arthritis, affecting 1.5 million US adults. Worldwide, 13 million people experience moderate-to-severe rheumatoid arthritis. Diagnosing rheumatoid arthritis can be difficult, but early diagnosis and treatment are associated with improved long-term health outcomes. (12) 

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What is Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints, causing inflammation, pain, and eventually joint damage and deformities. It is one of the most common types of inflammatory arthritis.

Autoimmunity occurs when the immune system, designed to protect the body from harmful and foreign invaders, mistakenly attacks and damages the body's own cells, tissues, and/or organs. In RA, the main target of this attack is the synovium, the lining of the membranes surrounding the joints.

RA can affect any joint in the body and generally attacks many joints simultaneously. The small joints of the hands and feet are most commonly affected; however, chronic inflammation can also negatively impact and damage other body parts, including the skin, eyes, lungs, heart, and blood vessels. (26) 

Rheumatoid Arthritis Signs & Symptoms

Patients with RA will experience periods when symptoms worsen, known as flares, and improve, known as remission.

Inflammatory arthritis is associated with classic inflammation symptoms, including pain, redness (erythema), warmth, swelling, and loss of function (21). The hallmark feature of RA is persistent symmetrical arthritis of multiple small joints within the hands and feet. Symptom onset is usually gradual and progressive, beginning with joint pain and stiffness. As RA progresses, affected joints become red, swollen, and deformed. Ulnar deviation, Boutonnière deformities, swan neck deformities, and rheumatoid nodules are common with late-stage RA. (5) 

About 40% of patients with RA will also present with clinical manifestations that extend beyond the joints. These can include fatigue, fever, loss of appetite, and weight loss. Inflammation can occur in other body systems, so patients may experience symptoms related to the heart, lungs, blood vessels, nerves, eyes, salivary glands, kidneys, and skin. (8, 26)

What Are the Possible Causes of Rheumatoid Arthritis?

In rheumatoid arthritis, the body's immune system mistakenly attacks the synovium, which is the lining of the membranes that surround the joints. This leads to inflammation of the synovium, causing joint pain, swelling, and stiffness. Over time, the persistent inflammation can damage the cartilage and bone within the joint, leading to joint deformities and functional limitations. (26)

The exact cause of rheumatoid arthritis is not fully understood, but it is believed to result from a combination of genetic and environmental factors. It is more common in women than men, with respective lifetime risks of 3.6% and 1.7%. RA risk also increases with age, with peak incidence occurring between 65-80 years of age. (4) 

Genetics play a significant role in the development of RA. The heritability of seropositive rheumatoid arthritis, meaning the patient has positive RA-associated antibodies on bloodwork, is up to 65%. The human leukocyte antigen (HLA) DRB1 gene alone contributes to RA risk by up to 37%. However, many other genetic variations have also been identified as contributing to RA risk. (4) 

While genetics significantly influence our susceptibility to autoimmune diseases, they do not provide an absolute prediction of disease development. The emergence of autoimmune diseases is a complex interplay between an individual's genetic makeup and the intricate web of environmental factors combined with epigenetic modifications. Epigenetics refers to the changes in gene expression that occur without altering the underlying DNA sequence. Diet, lifestyle, infections, stress, and environmental exposures can influence these epigenetic changes. This dynamic interaction between genetics, epigenetics, and environmental factors ultimately determines the likelihood of developing an autoimmune disease. (10, 18)

Cigarette smoking has been identified as the strongest environmental risk factor associated with RA. Other environmental and lifestyle triggers include toxic exposure to silica, asbestos, and textile dust; increased sugar consumption; never having given birth; exposure to secondhand smoke during childhood; obesity; and lower socioeconomic status. (4, 8) 

Changes in the composition of the gut microbiome have also been identified as a contributor to RA development. Patients with RA have decreased microbiome diversity, with increased certain bacteria, including Actinobacteria, Collinsella, Eggerthalla, and Faecalibacterium. These dysbiotic changes induce intestinal permeability, which has been linked to increased disease severity. Other factors perpetuating enhanced intestinal permeability include vitamin D deficiency, food sensitivities, exposure to mycotoxins and food chemicals, alcohol consumption, medications, and chronic stress (8, 26). (4) 

Functional Medicine Labs to Test for Root Cause of Rheumatoid Arthritis

Early diagnosis and appropriate treatment are crucial to help control the progression of rheumatoid arthritis and minimize its impact on daily life. Serologic and radiologic tests are used to look for evidence confirming the presence of RA in patients presenting with RA-like symptoms.  

Autoimmune Panel

RF (rheumatoid factor) and anti-CCP (anti-cyclic citrullinated peptide) are antibodies commonly tested for in individuals suspected of having rheumatoid arthritis. RF and anti-CCP can be present in the serum up to 10 years before the onset of clinical symptoms. RF is present in 80-90%, and anti-CCP in 70-80% of patients with RA. Patients with RA with positive RF, anti-CCP, or both are designated as having seropositive RA, which is associated with a higher risk of bone erosion. (1, 4)

Inflammatory Markers

Elevations of acute phase reactants ESR and CRP are consistent with the presence of inflammation and are directly proportional to the severity of inflammation (1). Measuring these markers over time helps monitor disease activity and treatment efficacy.  

Comprehensive Gut Assessment

A comprehensive stool assessment measures the amounts of various "good" and "bad" microorganisms to screen for dysbiosis, inflammatory and digestive markers, and zonulin, a protein indicative of leaky gut. Serum tests can also be ordered to evaluate intestinal permeability and provide insight into the underlying causes contributing to it. 

Food sensitivities can perpetuate leaky gut and contribute to developing autoimmunity and systemic inflammation. An ELISA test that detects antibodies in the blood can be a helpful tool in identifying food sensitivities so that customized elimination diets can be prescribed. 

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Conventional Treatment for Rheumatoid Arthritis

Treatment for rheumatoid arthritis aims to manage symptoms, reduce inflammation, prevent joint damage, and improve quality of life. Medications, physical therapy, lifestyle changes, and, in some cases, surgery may be recommended by healthcare professionals to help manage the condition. (8) 

Functional Medicine Treatment Protocol for Rheumatoid Arthritis

It's important to recognize that early pharmacologic treatment may be required to halt disease progression and prevent joint destruction and deformity. However, a functional medicine treatment protocol will also incorporate complementary and integrative modalities that address and correct the mechanisms fueling autoimmunity. This approach, therefore, aims to achieve longer-term clinical success by addressing autoimmunity with a root-cause approach. 

Therapeutic Diet and Nutrition Considerations for Rheumatoid Arthritis

RA is more prevalent in Western countries, where dietary intake is characterized by high intakes of poor-quality meat, saturated/trans fats, omega-6 fatty acids, and refined carbohydrates. This Western and inflammatory nutritional pattern has been associated with an increased risk of RA and obesity. (6)

Therefore, shifting away from these dietary patterns and towards an anti-inflammatory, whole-food, and nutrient-dense diet can assist in treating RA by reducing inflammation and supporting gut health. The autoimmune protocol (AIP) diet is commonly implemented in patients with autoimmune diseases. This diet eliminates known autoimmune dietary triggers, including grains, dairy, eggs, legumes, nightshades, nuts, seeds, processed foods, coffee, and alcohol. Instead, it emphasizes incorporating non-starchy vegetables, high-quality proteins, healthy fats, herbs, and spices into the diet. 

Supplements Protocol for Rheumatoid Arthritis

Nutraceutical and herbal supplements can support lifestyle and dietary modifications to reduce inflammation, palliate pain, modulate the immune system, and balance to intestinal microbiome. An example protocol is outlined below.

Multivitamin

Vitamins D, E, A, and C, zinc, and selenium are essential in supporting the immune system and gut barrier function; deficiencies can increase the susceptibility to immune dysfunction and infection. Using a high-potency multivitamin/mineral is an easy all-in-one way to supplement essential vitamins and minerals to prevent deficiency, support immune function, and heal the gut.

Dose: per label instructions

Duration: Ongoing

Curcumin

Curcumin is a natural compound found in turmeric and has been extensively researched for its potential anti-inflammatory and antioxidant properties. A 2023 systematic review and meta-analysis, including six publications and over 500 patients with RA, concluded that curcumin is an effective supplement for RA due to its ability to modulate the immune response, reduce inflammation, and provide symptomatic relief. 

Dose: 1,000 mg daily

Duration: 6 weeks-3 months

Boswellia serrata

Boswellia targets multiple signal transduction cascades that inhibit pro-inflammatory immunological chemicals, balance the immune system, and have anti-inflammatory effects (26). Boswellia administration in patients with RA reduces pain, swelling, morning stiffness, need for over-the-counter pain medications, ESR, and improvements in general health and well-being scores.  

Dose: 400-1,200 mg 2-3 times daily

Duration: 1-6 months

Probiotics

Using probiotic supplements to restore balance to the gut microbiome manipulates the gut-immune connection, regulating the immune system and modulating the inflammatory response, leading to improved clinical and symptom outcomes. Lactobacillus and Bifidobacterium species of bacteria are commonly present in lower concentrations in patients with RA than in healthy controls. Preliminary studies have suggested that using Lactobacillus, Bifidobacterium, and spore-based probiotics offers positive benefits in RA patients.

Dose & Duration will vary based on the individual; comprehensive stool testing can help tailor specific recommendations.

When To Retest Labs

Patients should be encouraged to follow up 6-8 weeks after implementing a recommended treatment protocol to discuss symptom changes and repeat serological testing to monitor progress.

Learning More About Rheumatoid Arthritis

• Magazine Article: Integrative Approaches to the Testing and Treatment of Rheumatoid Arthritis: A Comprehensive Review
• Case Study: 4 Things That Helped Laura Get Her Rheumatoid Arthritis Under Control
• Podcast: Autoimmune Diseases with Dr. Rob Silverman, Founder of Westchester Integrative Health Center
• Live Class: Early Detection of Autoimmunity with Immunosciences Comprehensive Panel

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Summary

Rheumatoid arthritis is an autoimmune, inflammatory arthritis responsible for causing joint destruction and disability. Early diagnosis and effective treatment are imperative to prevent the negative health consequences resulting from the undermanagement of this debilitating disease. Depending on disease severity and activity, pharmaceutical intervention may be required to achieve treatment goals. However, a functional medicine and root-cause treatment approach can be highly effective in modulating the immune system to dampen autoimmunity, reduce inflammation, and improve clinical outcomes.